25^th Nano Congress for Future Advancements

Biography

Biography: Robert K Prudhomme

Abstract

Biologics, the fastest-growing sector of the pharmaceutical marketplace, are an attractive class of therapeutics because of their impressive potency, high selectivity, and reduced off-target effects. But while the effectiveness of these drugs outclasses many of their small-molecule predecessors, administering biologics remains a challenge. Physiological barriers such as chemical digestion (when taken orally), rapid blood clearance (when injected), or thick pulmonary mucus (when inhaled) chemically or physically prevent biologics from reaching their targets and working as designed. To reduce the frequency of dosing, strategies of protecting these proteins and peptides within delivery vehicles have arisen, but the majority of these processes suffer from high losses and poor scalability. We here present a scalable and continuous method of encapsulating water-soluble charged biologics into polymeric nanoparticles. This is done by simultaneously reversibly ionically modifying the biologics of interest with hydrophobic counterions and controllably precipitating the newly-formed hydrophobic complex into nanoparticles via the polymer-directed Flash NanoPrecipitation technique. This combined technique, termed hydrophobic ion pairing Flash NanoPrecipitation (HIP-FNP), is applicable to a wide variety of peptides and proteins, both anionic and cationic. Importantly, the process is continuous, scalable, and achieves encapsulation efficiencies greater than 95%. We herein demonstrate encapsulation of two model proteins: the cationic enzyme lysozyme (MW 14,300 D) and the anionic protein ovalbumin (MW 42,700 D). By altering the identity or amount of hydrophobic counterion used, we can tune protein release rates, an important consideration for prolonged delivery. Importantly, we also show that the proteins’ activity has been retained throughout the processing steps. We believe this technique offers a route forward for improving the delivery of many biologic therapeutics and may improve patient comfort and compliance by simplifying dosing regimens.